Recommendations for UseThe IAPCOI recommends offering the vaccine to healthy children of parents who can afford the vaccine after explaining the pros and cons to the parents on a one-to one “named child” basis (Category 3). The vaccine is recommended for use in all individuals who can afford the vaccine in certain risk groups as enumerated below.
Vaccination with inactivated vaccines may also be offered to household contacts of patients with acute Hep A virus infection within 10 days of onset of illness in the index case. It may not always be effective under such circumstances when the contact has had the same source of infection as the index patient. If a decision to administer the vaccine is taken any of the licensed vaccines may be used as all have nearly similar efficacy and safety (exception for post exposure prophylaxis/immunocompromised patients where only inactivated vaccines may be used). Two doses 6 months apart are recommended for all vaccines. The manufacturers of the live attenuated vaccine claim that a single dose is sufficient for long term protection. Evidence supporting this claim is equivocal and hence till more information is available IAPCOI recommends two doses of even the live attenuated vaccine to primarily guard against primary vaccine failures. All Hep A vaccines are licensed for use in children aged 1 year or older. However in the Indian scenario it is preferable to administer the vaccines at age 18 months or more when maternal antibodies have completely declined. Vaccination at this age is preferable to immunization later as it is easier to integrate with the existing schedule, protects those who have no antibodies and protects children by the time children attend day care. Pre vaccination screening for Hepatitis A antibody is likely to be cost effective in children older than 10 years at which age the estimated seropositive rates exceed 50%. |
Adverse ReactionsIt includes local pain and local induration. |
Hepatitis A virus (HAV) infection is a relatively benign infection in young children. As many 85% of children below 2 years and 50% of those between 2-5 years infected with HAV are anicteric and may just have non-specific symptoms like any other viral infection. On the contrary, hepatitis A in adults is symptomatic in 70% to 95% with a mortality of 1%. The disease severity increases in those with underlying chronic liver disease.
Countries are classified as low/medium or highly endemic for Hepatitis A. In countries with high endemicity like India, most individuals acquire natural infection in childhood and burden of disease including incidence of outbreaks is low. As a shift occurs towards medium endemicity due to improvements in hygiene and sanitation a certain proportion of children remain susceptible till adulthood. Thus burden of symptomatic disease and incidence of outbreaks paradoxically increase.
Epidemiologic data from India though limited, suggests a shift in epidemiology of disease and HAV susceptibility in 30-40% of adolescents and adults belonging to the high socioeconomic class.
Inactivated Vaccines
Most of the currently available vaccines are derived from HM 175/GBM strains and grown on MRC5 human diploid cell lines. The virus is formalin inactivated and adjuvanted with aluminimum hydroxide. The vaccine is stored at 2 to 8° C.
The vaccines are given in a two dose schedule, 6 months apart intramuscularly. The adult formulation should be used after the recommended cut-off age of 15 years (AvaximTM) and 18 years (HavrixTM). Protective antibodies are seen in 95-100% 1 month after the 1st dose and almost 100% after the second dose. Serologic correlate of protection has been fixed at 20 mIU/ml.
The protective efficacy is around 90-100% and onset of protection is 2 weeks – 1 month after the 1st dose of the vaccine. The vaccine efficacy is lower in the elderly, immunocompromised, those with chronic liver disease, in transplant recipients and those with pre existing maternal antibodies.
The vaccine may be safely given with other childhood vaccines and interchange of brands is permitted though not routinely recommended. Immunity is lifelong due to anamnestic response and no boosters are recommended at present in the immunocompetent. Adverse reactions are minor and usually include local pain and swelling.
A liposomal adjuvanted hepatitis A vaccine derived from the RG-SB strain, harvested from disrupted MRC-5 cells and inactivated by formalin is now available (Havpur). The liposome adjuvant is immunopotentiating reconstituted influenza virosome (IRIV) composed of phosphatidylcholine, phosphatidylethanolamine and hemagglutinin from an H1N1 strain of influenza virus. The efficacy and safety profile is nearly similar to the other inactivated vaccines.
Combination Hep A and Hep B vaccines are also available to be used in those who have not been vaccinated for Hep B previously. These are available in both adult and pediatric formulations and are discussed separately under combination vaccines.
Live Attenuated Vaccine
This vaccine is derived from the H2 strain of the virus attenuated after serial passage in Human Diploid Cell (KMB 17 cell line). It has been in use in China since the 1990’s in mass vaccination programs. The vaccine meets requirements of the Chinese drug authority and the WHO. It is also now licensed and available in India (Biovac A).
The recommended dose in 1 ml SC (10 (6.5) CCID50/ml) in children aged 1-15 years. Immunogenicity studies with single dose show seroconversion rates of more than 98% 2 months after vaccination and persistence of protective antibodies in more than 80% of vaccines at 10 year follow up. Uncontrolled studies show an efficacy of almost 100% sustained over 10 years despite decline in seroprotection rates and antibody titers.
Recent immunogenicity
studies from India have shown > 95% seroconversion,
6 weeks following single dose of the vaccine and sustained
protection over at least 2 years, though antibody titers are
significantly lower than those achieved with inactivated
vaccines though above the protective level. Some observational
Chinese studies have reported inability of single dose of the
vaccine to protect against subclinical infection. Chinese studies
with 2 doses of the vaccine have shown better seroprotection
rates and higher antibody titers over prolonged follow up as
compared to historical controls who received single dose. No
horizontal transmission or serious adverse effects have been
noted. The vaccine is not effective as post-exposure prophylaxis.